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利用计算工具揭示脓肿分枝杆菌泛基因组:洞察进化动态和生活方式。

Unlocking the Mycobacteroides abscessus pan-genome using computational tools: insights into evolutionary dynamics and lifestyle.

机构信息

Department of Botany, Ramananda College, Life Sciences Block, Bishnupur, West Bengal, 722122, India.

出版信息

Antonie Van Leeuwenhoek. 2024 Nov 23;118(1):30. doi: 10.1007/s10482-024-02042-z.

DOI:10.1007/s10482-024-02042-z
PMID:39579164
Abstract

Mycobacteroides abscessus is a non-tuberculous mycobacteria implicated in causing lung infections. It is difficult to control owing to resistance to antibiotics and disinfectants. This work was aimed at comprehending: the pan-genome architecture, evolutionary dynamics, and functionalities of pan-genome components linked to COGs and KEGG. Around 2802 core genes were present in each strain of the M. abscessus genome. The number of accessory genes ranged from 1615 to 2481. The open pan-genome of M. abscessus was attributed to the accessory genes underlining its adaptability in the host. Phylogenetic analysis revealed cluster-based relationships and highlighted factors shaping variability and adaptive capabilities. Transcription, metabolism, and pathogenic genes were vital for M. abscessus lifestyle. The accessory genes contributed to the diverse metabolic capability. The incidence of a significant portion of secondary metabolite biosynthesis genes provided insights for investigating their biosynthetic gene clusters. Additionally, a high proportion of xenobiotic biodegradation genes highlighted potential metabolic capabilities. In silico screening identified a potential vaccine candidate among hypothetical proteins in COGs. Functional analysis of M. abscessus pan-genome components unveiled factors associated with virulence, pathogenicity, infection establishment, persistence, and resistance. Notable amongst them were: MMPL family transporters, PE-PPE domain-containing proteins, TetR family transcriptional regulators, ABC transporters, Type-I, II, III, VII secretion proteins, DUF domain-containing proteins, cytochrome P450, VapC family toxin, virulence factor Mce family protein, type II toxin-antitoxin system. Overall, these results enhanced understanding of the metabolism, host-pathogen dynamics, pathogenic lifestyle, and adaptations. This will facilitate further investigations for combating infections and designing suitable therapies.

摘要

脓肿分枝杆菌是一种非结核分枝杆菌,与肺部感染有关。由于对抗生素和消毒剂的耐药性,它很难控制。这项工作旨在理解:泛基因组结构、进化动态以及与 COGs 和 KEGG 相关的泛基因组成分的功能。每个脓肿分枝杆菌菌株中都存在约 2802 个核心基因。辅助基因的数量从 1615 到 2481 不等。脓肿分枝杆菌的开放泛基因组归因于辅助基因,这些基因强调了其在宿主中的适应性。系统发育分析揭示了基于聚类的关系,并强调了塑造变异性和适应能力的因素。转录、代谢和致病基因对脓肿分枝杆菌的生活方式至关重要。辅助基因有助于多样化的代谢能力。大量次生代谢产物生物合成基因的存在为研究其生物合成基因簇提供了依据。此外,高比例的异生物质生物降解基因突出了潜在的代谢能力。在 COGs 中的假设蛋白中,计算机筛选鉴定了一个潜在的疫苗候选物。脓肿分枝杆菌泛基因组成分的功能分析揭示了与毒力、致病性、感染建立、持续存在和耐药性相关的因素。其中值得注意的是:MMPL 家族转运蛋白、PE-PPE 结构域蛋白、TetR 家族转录调节因子、ABC 转运蛋白、I 型、II 型、III 型、VII 型分泌蛋白、DUF 结构域蛋白、细胞色素 P450、VapC 家族毒素、毒力因子 Mce 家族蛋白、II 型毒素-抗毒素系统。总体而言,这些结果增强了对代谢、宿主-病原体动态、致病生活方式和适应的理解。这将有助于进一步研究对抗感染和设计合适的治疗方法。

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